Medication compliance is an important medical process, and useful methods are needed to measure compliance in clinical practice. Interview, pill count, and serum digoxin concentration (SDC) were compared in 173 patients prescribed digoxin to determine (1) feasibility, ease, timeliness; (2) reasons for noncompliance; and (3) validity of interview and pill count compared with SDC. All patients were interviewed; among 33 (19%) not taking their medication correctly, nine (5%) did not know how. Pill counts were possible for 68 patients (39%). One patient had a correct pill count. Steady-state SDCs were obtained for 143 patients (83%), but were not available during patients' visits. The SDCs for 25 patients were less than 0.50 ng/mL. Interviews correlated with SDCs, pill counts did not. Pill counts and SDCs required telephoning patients before appointments. In clinical practice, interview may be the most useful methof of measuring medication compliance.